Individuals with psychosis present a reduced lung diffusion capacity and early spirometry alterations: Results from a cross-sectional study.

OBJECTIVE: Individuals with psychosis present a greater prevalence of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). These chronic respiratory diseases are preceded by early lung function alterations; such as preserved ratio impaired spirometry (PRISm) or normal spirometry but low diffusion capacity of the lung for carbon monoxide (DLCO). However, there is no previous evidence on these lung function alterations in psychosis. The aim of this study is to evaluate the risk of having spirometry and DLCO alterations in subjects with psychosis compared with a control group. METHODS: Cross-sectional study on a cohort of 170 individuals including 96 subjects with psychosis and 74 sex-age-and smoking habit matched healthy controls. All subjects were under 60 years-old, and without COPD or asthma. Respiratory function was evaluated through spirometry. Clinical characteristics and DLCO values were recorded. RESULTS: Patients with psychosis showed lower spirometry results, both in terms of absolute and percentage of Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1). Absolute and percentage levels of diffusion were also lower in patients with psychosis. The percentage of individuals with DLCO<80% was higher among patients with psychosis (75% vs. 40%, p < 0.001). And the prevalence of PRISm was higher among patients with psychosis (10.4% vs. 1.4%, p < 0.001). Multivariate logistic regression analysis indicated that psychosis was an independent predictor of DLCO<80% (OR 5.67, CI95% 1.86-17.27). CONCLUSION: Patients with psychosis and females had early alterations in lung function. These results suggest that early screening for lung disease should be encouraged in psychosis.

Increased risk of early lung function alterations in people with psychosis: A cross-sectional case-control study.

BACKGROUND: Tobacco smoking has been described as the main cause of chronic obstructive pulmonary disease (COPD) and this habit is clearly more frequent among individuals with psychosis than in the general population, with rates reaching up to 60%. However, little attention has been focused on the association of COPD and psychosis. We aimed to explore the risk of presenting early lung function alterations in a group of individuals with psychosis. METHODS: Following an observational cross-sectional design we studied a cohort of individuals with established psychosis (N=128), and compared them with a sex, age, and smoking habit matched control group (N=79). We evaluated respiratory symptoms by means of mMRC, CAT and Dyspnea-12 scales. And lung function through spirometry tests. RESULTS: Individuals with psychosis presented more respiratory symptoms than controls. Similarly, we observed significant differences in the lung function tests between these two groups, where individuals with psychosis presented worse results in most of the spirometry mean values (FEV1 or forced expiratory volume in the first one second: 3.29L vs. 3.75L, p<0.001; forced vital capacity or FVC: 4.25L vs. 4.72L, p=0.002; and FEV1/FVC ratio: 0.78 vs. 0.80, p=0.052). Patients also presented worse values of lung diffusion, with lower diffusing capacity for carbon monoxide (DLCO) than controls (6.95 vs. 8.54mmol/min/kPa, p<0.001). CONCLUSIONS: The individuals with psychosis in our study presented greater respiratory symptoms and poorer lung function measured through spirometry. These signs have been described as early signs of COPD.

Cognitive reserve as a moderator of outcomes in five clusters of first episode psychosis patients: a 10-year follow-up study of the PAFIP cohort.

BACKGROUND: Cognitive reserve (CR) has been associated with the development and prognosis of psychosis. Different proxies have been used to estimate CR among individuals. A composite score of these proxies could elucidate the role of CR at illness onset on the variability of clinical and neurocognitive outcomes. METHODS: Premorbid intelligence quotient (IQ), years of education and premorbid adjustment were explored as proxies of CR in a large sample (N = 424) of first-episode psychosis (FEP) non-affective patients. Clusters of patients were identified and compared based on premorbid, clinical and neurocognitive variables at baseline. Additionally, the clusters were compared at 3-year (N = 362) and 10-year (N = 150) follow-ups. RESULTS: The FEP patients were grouped into five CR clusters: C1 (low premorbid IQ, low education and poor premorbid) 14%; C2 (low premorbid IQ, low education and good premorbid adjustment) 29%; C3 (normal premorbid IQ, low education and poor premorbid adjustment) 17%; C4 (normal premorbid IQ, medium education and good premorbid adjustment) 25%; and C5 (normal premorbid IQ, higher education and good premorbid adjustment) 15%. In general, positive and negative symptoms were more severe in the FEP patients with the lowest CR at baseline and follow-up assessments, while those with high CR presented and maintained higher levels of cognitive functioning. CONCLUSIONS: CR could be considered a key factor at illness onset and a moderator of outcomes in FEP patients. A high CR could function as a protective factor against cognitive impairment and severe symptomatology. Clinical interventions focused on increasing CR and documenting long-term benefits are interesting and desirable.

Long-term mental health impact of COVID-19 on primary care health workers in northern Spain: Results from a two-phase longitudinal study.

Background: COVID-19 pandemic has affected the mental health of the general population, and in particular of health professionals. Primary care personnel are at greater risk due to being highly exposed to the disease and working regularly in direct contact with patients suffering COVID-19. However, there is not sufficient evidence on the long-term psychological impact these professionals may suffer. We aimed to explore the long-term psychological impact of COVID-19 on primary care professionals. Methods: We applied a two-phase design; a self-reported psychopathology screening (PHQ-9, GAD-7, ISI and IES-R) in phase-1, and a specialised psychiatric evaluation (MINI, HDRS and STAI) in phase-2 to confirm phase-1 results. Evaluations were carried at the beginning of the pandemic (May-June 2020) (n = 410) and one year later (n = 339). Chi-square, ANOVA and logistic regression tests were used for statistical analyses. Results: Primary care professionals presented high rates of depression, anxiety and psychological distress, measured by PHQ-9, GAD-7 and IES-R respectively, during the pandemic. Depressive symptoms' severity (PHQ-9: 7.5 vs 8.4, p = 0.013) increased after one year of COVID-19 pandemic. After one year nearly 40% of subjects presented depression. Being women, having suffered COVID-19 or a relative with COVID-19, and being a front-line professional were risk factors for presenting depression and anxiety. Conclusion: Primary Care professionals in Cantabria present a poor mental health during COVID-19 pandemic, which has even worsened at long-term, presenting a greater psychopathology severity one year after. Thus, it is critical implementing prevention and early-treatment programmes to help these essential professionals to cope with the pandemic.

Antecedentes: La pandemia de COVID-19 ha afectado la salud mental de la población general, y en particular de los sanitarios. El personal de atención primaria tiene mayor riesgo por estar más expuesto a la enfermedad y trabajar regularmente en contacto directo con pacientes que padecen COVID-19. Sin embargo, no existe suficiente evidencia sobre el impacto psicológico a largo plazo que pueden sufrir estos profesionales. Nuestro objetivo fue explorar el impacto psicológico a largo plazo de COVID-19 en los profesionales de atención primaria. Métodos: Se aplicó un diseño en dos fases; un cribado de psicopatología a través de cuestionarios autoaplicados (PHQ-9, GAD-7, ISI e IES-R) en la fase 1, y una evaluación psiquiátrica especializada (MINI, HDRS y STAI) en la fase 2 para confirmar los resultados de la fase 1. Las evaluaciones se realizaron al inicio de la pandemia (mayo-junio de 2020) (n = 410) y un año después (n = 339). Se utilizaron pruebas de X 2, ANOVA y regresión logística para los análisis estadísticos. Resultados: Los profesionales de atención primaria presentaron índices elevados de depresión, ansiedad y malestar psicológico, medidos por PHQ-9, GAD-7 e IES-R, respectivamente, durante la pandemia. La severidad de los síntomas depresivos (PHQ-9: 7,5 vs 8,4; p = 0,013) aumentó tras un año de pandemia COVID-19. Después de un año, casi 40% de los sujetos presentaron depresión. El sexo femenino, haber padecido COVID-19 o tener un familiar con COVID-19 y ser profesional de primera línea fueron factores de riesgo para presentar depresión y ansiedad. Conclusiones: Los profesionales de Atención Primaria en Cantabria presentaron una mala salud mental durante la pandemia de COVID-19, la cual además empeoró a largo plazo, presentando una mayor gravedad los síntomas un año después. Por lo tanto, es fundamental implementar programas de prevención y tratamiento temprano para ayudar a estos profesionales esenciales a hacer frente a la pandemia.

Metabolic syndrome and related factors in a large sample of antipsychotic naïve patients with first-episode psychosis: 3 years follow-up results from the PAFIP cohort.

BACKGROUND: Latest studies in patients with first episode psychosis (FEP) have shown alterations in cardiovascular, immune and endocrinological systems. These findings could indicate a systemic onset alteration in the metabolic disease as opposed to justifying these findings exclusively by antipsychotics' side effects and long-term lifestyle consequences. In any case, this population is considered at higher risk for developing cardiometabolic disorders than their age-matched peers. METHODS: This is a prospective longitudinal study. Metabolic syndrome (MetS) prevalence between 244 subjects with FEP and 166 controls at 3 years was compared. Additionally, we explored whether baseline differences in any of the MetS components according to Adult Treatment Panel III definition and prescribed antipsychotic could help to predict the MetS development at 3 years. RESULTS: Patients with FEP present a similar baseline prevalence of MetS (6.6% vs 5.4%, p=0.320), according to ATP-III criteria. but with a higher prevalence of metabolic alterations than controls before the start of antipsychotic treatment. At 3-years follow-up the MetS prevalence had increased from 6.6% to 18.3% in the FEP group, while only from 5.4% to 8.1% in the control group. The multivariate model showed that, before antipsychotic exposure, a baseline altered waist circumference WC (OR=1.1, p=0.011), triglycerides (OR=1.1, p=0.043) and high-density lipoprotein HDL (OR=0.9, p=0.008) significantly predicted the presence of MetS at 3-years. We propose a predictive model of MetS at 3 years in 244 drug-naïve FEP patients. CONCLUSION: We found that altered WC, HDL and triglycerides at baseline predicted the presence of full MetS after 3-years of initiating antipsychotic treatment. Our findings support the need for interventions to improve factors related to the physical health of FEP individuals.

Aripiprazole vs Risperidone Head-to-Head Effectiveness in First-Episode Non-Affective-Psychosis: A 3-Month Randomized, Flexible-Dose, Open-Label Clinical Trial.

BACKGROUND: Antipsychotic choice for the acute phase of a first episode of psychosis (FEP) is of the utmost importance since it may influence long-term outcome. However, head-to-head comparisons between second-generation antipsychotics remain scarce. The aim of this study was to compare the effectiveness in the short term of aripiprazole and risperidone after FEP outbreak. METHODS: From February 2011 to October 2018, a prospective, randomized, open-label study was undertaken. Two hundred-sixty-six first-episode drug-naïve patients were randomly assigned to aripiprazole (n = 136) or risperidone (n = 130) and followed-up for 12 weeks. The primary effectiveness measure was all-cause treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted to assess clinical efficacy. RESULTS: The overall dropout rate at 12 weeks was small (6.39%). Effectiveness measures were similar between treatment arms as treatment discontinuation rates (χ 2 = 0,409; P = .522), and mean time to all-cause discontinuation (log rank χ 2 = -1.009; P = .316) showed no statistically significant differences. Despite no statistically significant differences between groups regarding clinical efficacy, aripiprazole required higher chlorpromazine equivalent dosage (χ 2 = 2.160; P = .032) and extended mean time (W = 8183.5; P = .008) to reach clinical response. Sex-related adverse events and rigidity were more frequent in the risperidone group, whereas sialorrhea was on the aripiprazole group. CONCLUSIONS: No differences regarding effectiveness were found between aripiprazole and risperidone for the short-phase treatment of FEP. Despite the importance of efficacy during this phase, differences in side effect profiles and patient's preferences are essential factors that may lead clinical decisions for these patients. CLINICALTRIALS.GOV: NCT02532491. Effectiveness of Second-Generation Antipsychotics in First Episode Psychosis Patients: 1-year Follow-up (PAFIP3_1Y).

Naturalistic study on the use of clozapine in the early phases of non-affective psychosis: A 10-year follow-up study in the PAFIP-10 cohort.

Clozapine is seldom prescribed in treatment-resistant schizophrenia (TRS) patients during early phases of the illness. We aimed to examine the pathway and patterns and the impact of clozapine use in patients with TRS who were followed up for 10 years after the first outbreak of the illness. Data were obtained retrospectively from an epidemiological cohort of first episode schizophrenia patients (n = 218) who had been treated in a specialized intervention program (PAFIP). Out of 218, 35 (16%) individuals were on clozapine at 10-year assessment, while 183 (84%) were taking other antipsychotics. Among those 183 psychosis subjects who were not on clozapine, 13 (7.1%) met criteria for TRS. In the clozapine group, ten (28.6%) met criteria for early-TR and twenty-five (71.4%) met criteria for late-TR. Before clozapine treatment was initiated, the median number of days under other antipsychotic treatment was 1551 days (IQR = 1715) and the median time that subjects remained on clozapine was 6.3 years (IC95%: 5.49-7.20). At 10 years, we found that those individuals taking clozapine had higher CGI total scores (F = 12.0, p = 0.001) and SANS total scores (F = 9.27, p = 0.003) than subjects taking other antipsychotics after correcting for baseline values. Interestingly, when performing these analyses at 10 years between subjects taking clozapine (n = 35) and subjects who despite meeting TRS criteria were not taking clozapine (n = 13), we found that subjects taking clozapine had significantly lower total scores on all clinical scales compared with subjects who met TRS criteria and were not taking clozapine (p values < 0.05). TRS patients who took the longest time to start clozapine (third tertile) showed significantly higher CGI scores at 10-year follow-up compared to those who initiated clozapine earlier (first tertile) (t = 2.60; p = 0.043). Our findings reinforce the need of a timely assessment of treatment-resistant criteria in early schizophrenia patients and highlight the long-term benefits of an early introduction of clozapine on those patients meeting treatment-resistant criteria.

Elevated risk of liver steatosis in first-episode psychosis patients: Results from a 3-year prospective study.

BACKGROUND: Cardiometabolic disorders are largely responsible for excess mortality in schizophrenia. Non-alcoholic fatty liver disease (NAFLD) is increasingly relevant in the development of metabolic risk factors that have been associated with antipsychotic treatment. We aimed to assess the incidence of NAFLD and metabolic disturbances during the first 3 years of antipsychotic treatment in patients with first episode of psychosis (FEP), and compare it with the incidence in a control group. METHODS: Data were obtained from patients with psychosis (n = 160) and healthy controls (n = 66) included in the Cantabria's clinical and research program on FEP (PAFIP) from 2012 to 2018. Fatty Liver Index (FLI) was used to estimate the amount of fat in the liver. FLI has been validated for the diagnosis of NAFLD against different standards such as liver ultrasound and biopsy. FLI and metabolic parameters were registered at baseline, 3 months and then yearly for 3 years. RESULTS: At the end of the follow-up (3-years), 21.9 % of patients with psychosis developed a FLI ≥ 60, suggestive of liver steatosis, compared to only a 3 % of subjects within the control group (X2 = 12.120; p < 0.001). In the FEP patients group, developing a FLI ≥ 60 was statistically associated with significant increments in metabolic parameters, and with Metabolic Syndrome (MetS) (X2 = 16.151; p < 0.001) and high blood pressure (X2 = 10.654; p = 0.001). CONCLUSIONS: Having a first episode of non-affective psychosis was significantly associated with developing liver steatosis (FLI ≥ 60) in the first three years after initiating antipsychotic treatment. The results highlight the importance of early screening the emergence of NAFLD in schizophrenia patients.

Aripiprazole and Risperidone Present Comparable Long-Term Metabolic Profiles: Data From a Pragmatic Randomized Controlled Trial in Drug-Naïve First-Episode Psychosis.

OBJECTIVE: Aripiprazole and risperidone are 2 of the most used second-generation antipsychotics (SGAs) worldwide. Previous evidence shows a similar effect of these SGAs on weight and metabolic changes in the short term. However, a longer period is necessary for a better assessment of the SGA´s metabolic profile. We aimed to compare the long-term (1-year) metabolic profile of these 2 antipsychotics on a sample of drug-naïve first episode-psychosis (FEP) patients. METHODS: A total 188 drug-naïve patients, suffering from a first episode of non-affective psychosis (FEP), were randomly assigned to treatment with either aripiprazole or risperidone. Weight and glycemic/lipid parameters were recorded at baseline and after 1-year follow-up. RESULTS: We observed significant weight increments in both groups (9.2 kg for aripiprazole and 10.5 kg for risperidone) after 1 year of treatment. Despite this, weight and body mass index changes did not significantly differ between treatment groups (P > .05). Similarly, both treatment groups presented similar metabolic clinical impact with a comparable increase in the proportion of participants meeting criteria for metabolic disorders such as obesity or hypercholesterolemia, but not for metabolic syndrome (Δ9.2% vs Δ4.3%) or hypertriglyceridemia (Δ21.9% vs Δ8.0%), where aripiprazole showed worse outcomes than risperidone. CONCLUSION: This study shows that aripiprazole and risperidone share a similar long-term metabolic profile. After 1 year of antipsychotic treatment, drug-naïve FEP patients in both treatment groups presented a significant increase in weight and metabolic changes, leading to a greater prevalence of metabolic disorders.

Stability of schizophrenia diagnosis in a 10-year longitudinal study on first episode of non-affective psychosis: Conclusions from the PAFIP cohort.

OBJECTIVE: To evaluate the 10-year stability of schizophrenia diagnosis in a cohort of first-episode psychosis (FEP) patients and the factors associated with it. METHODS: Changes in diagnosis of 209 FEP patients were described during 10 years of follow-up. Related factors with maintenance or change of schizophrenia diagnosis were evaluated in prospective and retrospective approaches through binary logistic regressions, ROC and survival curves. RESULTS: Out of the 209 patients, 126 were diagnosed of schizophrenia 6 months after their inclusion in the clinical program. Prospective analyses showed that eight of those 126 schizophrenia patients had changed to a different diagnosis after 10 years, and predictors of change were better childhood premorbid adjustment, less severity of clinical global impression at baseline, and diagnosis of comorbid personality disorder during follow-up. Retrospectively, out of the 154 patients with schizophrenia in the 10-year assessment, 36 had a different diagnosis at baseline, and those factors related to a different prior diagnosis than schizophrenia were better socioeconomic status and shorter duration of untreated psychosis (DUP). A survival analysis on the timing of schizophrenia diagnosis showed that male gender and longer DUP were predictors of earlier definite diagnosis. CONCLUSIONS: Diagnostic stability of schizophrenia in our FEP sample is high, especially prospective stability, and the group of patients with diagnostic change corresponded to a milder psychopathological profile before and at the onset of disease. Moreover, we observed a cautious attitude in the diagnosis of schizophrenia in patients with shorter DUP who had schizophrenia diagnosis after 10 years.

Prolactin, metabolic and immune parameters in naïve subjects with a first episode of psychosis.

BACKGROUND: Prolactin (Prl) is a pleiotropic hormone initially described for its regulation of lactation in mammals but later associated with metabolic and immune homeostasis, stress, inflammatory response and human behavior. Its regulation through dopamine receptors highlights its importance in psychiatry mostly because hyperprolactinemia is a common secondary side effect of dopamine antagonists. Despite its undeciphered patho-physiological mechanisms, hyperprolactinemia in naïve psychosis patients has been widely described. Its consequences might underlie the increased morbidity and early mortality found in naïve subjects as described in the general population where prolactin values have been correlated with inflammatory, immune and metabolic parameters. METHODS: We aimed to evaluate the correlation between prolactin values and other biochemical parameters (C-reactive Protein-CrP, blood cell count, lipid and hepatic profile, fasting glucose) in a cohort of first episode psychosis naïve subjects (N = 491) stratified by sex. Regression analyses with confounders were performed to evaluate the association. FINDINGS: Prl displayed significant correlations with C-Reactive Protein (CrP), Low-Density Lipoprotein (LDL), Aspartate Transaminase (AST) for females and High-Density Lipoprotein (HDL) and eosinophil count for males. However, and despite previous specific sex correlations, significant associations were described for CrP, HDL, LDL, AST and ALT without sex interaction and despite confounders such as age, Body Mass Index or smoking status. CONCLUSIONS: Our results show a specific relation of Prl with immune and metabolic parameters describing a heterogeneous pattern. Our results suggest that prolactin might underlie the excess of morbidity and early mortality in naïve patients through a specific pathway.

Active psychosis and pro-inflammatory cytokines in first-episode of psychosis.

Higher levels of pro-inflammatory cytokines are consistently found in the serum of first episode psychosis (FEP) patients and this immune dysfunction could contribute to neural harm. On the other hand, lengthy periods of active psychosis during the early phases of the illness appear to be associated to worst functional outcome. We aim to explore the possible relationship between lengthy periods of active psychosis during early phases of the illness and the levels of pro-inflammatory cytokines. This is a prospective clinical study consisting of a 3-year clinical follow-up. We assessed the relation between the duration of active psychosis in patients with FEP and the serum levels of 21 cytokines at baseline and 3 months after initiating antipsychotic medication. We used the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. The sample consisted of 59 patients with a FEP. The percentage of variation of the serum levels of the chemokine MIP-3α during the first 3 months of antipsychotic treatment and the score in negative psychotic symptoms 3 months after the initiation of antipsychotic medication, acted as predictors of the initial time to remission of positive psychotic symptoms. Our findings open the possibility to investigating the potential use of the variation in chemokine MIP-3α serum levels during the first months of antipsychotic treatment to identify a subtype of FEP patients that could benefit from an add-on treatment with immune modulators. CLINICALTRIALS.GOV ID: NCT02897167. DATE OF FIRST REGISTRATION: September 13, 2016. "Study of the Activation of Proinflammatory Pathways of Toll-like Receptors in Schizophrenia Patients (PAFIP_TLR)". https://clinicaltrials.gov/ct2/show/NCT02897167.

Dissecting the functional outcomes of first episode schizophrenia spectrum disorders: a 10-year follow-up study in the PAFIP cohort.

BACKGROUND: The aim of the current study was to examine the heterogeneity of functional outcomes in first episode psychosis (FEP) patients and related clinical, neurocognitive and sociodemographic factors using a cluster analytic approach. METHOD: A large sample of FEP patients (N = 209) was functionally reassessed 10 years after the first contact with an early intervention service. Multiple baseline, 3-year and 10-year follow-up variables were explored. RESULTS: The cluster analysis emphasized the existence of six independent clusters of functioning: one cluster was normal overall (42.16%), two clusters showed moderate interpersonal (9.63%) or instrumental (12.65%) deficits, two clusters showed more severe interpersonal (12.05%) or interpersonal and instrumental (13.85%) deficits and there was a significantly overall impaired cluster (9.63%). Cluster comparisons showed that several baseline and follow-up factors were differentially involved in functional outcomes. CONCLUSIONS: The current study demonstrated that distinct clusters of functioning in FEP patients can be identified. The fact that a variety of profiles was observed contributes to a better understanding of the nature of the heterogeneity characterizing FEP patients and has clinical implications for developing individualized treatment plans.

Treatment Discontinuation Impact on Long-Term (10-Year) Weight Gain and Lipid Metabolism in First-Episode Psychosis: Results From the PAFIP-10 Cohort.

BACKGROUND: Patients with a first episode of psychosis (FEP) are at higher risk of gaining weight and presenting metabolic disturbances, partly related to antipsychotic exposure. Previous studies suggest that treatment discontinuation might have a positive impact on weight in schizophrenia. The aim of this study was to evaluate the effect of treatment discontinuation on weight and metabolic changes in a FEP cohort. METHODS: A total of 209 FEP patients and 57 healthy controls were evaluated at study entry and prospectively at 10-year follow-up. Anthropometric measures and, clinical, metabolic, and sociodemographic data were collected. RESULTS: Patients discontinuing antipsychotic treatment presented a significantly lower increase in weight and better metabolic parameter results than those still on antipsychotic treatment at 10-year follow-up. CONCLUSIONS: Treatment discontinuation had a positive effect on the weight and metabolic changes observed in FEP patients; however, this effect was not sufficient to reaching a complete reversal to normal levels.

Understanding sex differences in long-term outcomes after a first episode of psychosis.

While sex differences in schizophrenia have long been reported and discussed, long-term sex differences in outcomes among first episode of psychosis (FEP) patients in terms of the efficacy of Early Intervention Services (EIS) has been an under-explored area. A total of 209 FEP patients (95 females and 114 males) were reassessed after a time window ranging from 8 to 16 years after their first contact with an EIS program (PAFIP) that we will call the 10-year PAFIP cohort. Multiple clinical, cognitive, functioning, premorbid, and sociodemographic variables were explored at 1-year, 3-year and 10-year follow-ups. At first contact, females were older at illness onset, had higher premorbid adjustment and IQ, and were more frequently employed, living independently, and accompanied by a partner and/or children. Existence of a schizophrenia diagnosis, and cannabis and alcohol consumption were more probable among men. During the first 3 years, women showed a significantly better response to minimal antipsychotic dosages and higher rates of recovery than men (50% vs. 30.8%). Ten years later, more females continued living independently and had partners, while schizophrenia diagnoses and cannabis consumption continued to be more frequent among men. Females also presented a lower severity of negative symptoms; however, functionality and recovery differences did not show significant differences (46.7% vs. 34.4%). Between the 3- and 10-year follow-up sessions, an increase in dosage of antipsychotics was observed. These results suggest that the better outcomes seen among women during the first 3 years (while they were treated in an EIS) were in the presence of more favourable premorbid and baseline characteristics. After an average period of 10 years, with the only difference being in negative symptoms course, outcomes for women approximated those of men, drawing particular attention to the increase in dosage of antipsychotic medication once FEP patients were discharged from the EIS program towards community-based services. These findings help to pose the question of whether it is advisable to target sexes and lengthen EIS interventions.

A 3-year prospective study on the metabolic effect of aripiprazole, quetiapine and ziprasidone: A pragmatic clinical trial in first episode psychosis patients.

Schizophrenia is a severe brain disorder with an excess morbidity and mortality partly due to a higher incidence of metabolic disturbances and cardio-vascular events. The exposure to antipsychotic treatment has been observed linked to these metabolic abnormalities. This study explores the metabolic effects of aripiprazol, quetiapine and ziprasidone in drug-naïve patients with a first-episode of psychosis, at long-term. Two-hundred and two patients with first-episode of psychosis were included in the study. Patients were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Clinical, sociodemographic and anthropometric measures, as well as lipid and glyceamic parameters, were recorded at baseline and after three years of initiating antipsychotic treatment. Body weight and BMI increased significantly after 3 years of follow-up (F = 35.0, p<0.001; and F = 37.6, p<0.001, respectively). Most of the increase in weight occurred within the first year of treatment. The proportion of patients meeting criteria for obesity (5.6% vs 25.7%; p<0.001), hypercholesterolemia (23.2% vs 41.7%; p<0.001) and hypertriglyceridemia (5.8% vs 23.0%; p<0.001) increased significantly. Head-to-head comparisons between antipsychotic groups revealed that the ziprasidone group presented significantly smaller increments in weight (p = 0.034) and BMI (p = 0.020) than aripiprazole group. After 3 years of having presented a first episode of psychosis, patients show significant increments in body weight and BMI, as well as in lipid and glycaemic parameters leading to clinical metabolic disturbances. In this context, the first year is the critical period for weight gain and development of metabolic changes. In this study, ziprasidone produced smaller weight gain than aripiprazole.

Expression and Functionality Study of 9 Toll-Like Receptors in 33 Drug-Naïve Non-Affective First Episode Psychosis Individuals: A 3-Month Study.

Toll-like receptors (TLRs) are a pivotal component of the innate immune system that seem to have a role in the pathogenesis of psychosis. The purpose of this work was to compare the expression and functionality of 9 TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells, and T cells) between 33 drug-naïve first-episode psychosis (FEP) individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment. The expression of TLRs 1-9 were assessed by flow cytometry. For the assessment of the TLR functionality, cells collected in sodium heparin tubes were polyclonally stimulated for 18 h, with different agonists for human TLR1-9. The results of our study highlight the role that TLR5 and TLR8 might play in the pathophysiology of psychosis. We found a lower expression of these receptors in FEP individuals, regarding healthy volunteers at baseline and after 3-month of treatment on the three PBMCs subsets. Most TLRs showed a lower functionality (especially reduced intracellular levels of TNF-α) in patients than in healthy volunteers. These results, together with previous evidence, suggest that individuals with psychosis might show a pattern of TLR expression that differs from that of healthy volunteers, which could vary according to the intensity of immune/inflammatory response.

Antipsychotic Treatment Effectiveness in First Episode of Psychosis: PAFIP 3-Year Follow-Up Randomized Clinical Trials Comparing Haloperidol, Olanzapine, Risperidone, Aripiprazole, Quetiapine, and Ziprasidone.

BACKGROUND: Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. METHOD: From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. RESULTS: The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea. CONCLUSIONS: Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030.