Anthropometry in antipsychotic-naïve first-episode psychosis patients: An exploratory approach to the role of environmental early life events in two independent samples.

BACKGROUND: Patients with schizophrenia exhibit a reduced life expectancy mainly due to medical-related pathologies which might have been initiated due to stressful events during fetal development. Indeed, intra-uterus growth patterns predict anthropometric measures in adulthood, describing risk factors for schizophrenia and metabolic disorders. We aim to evaluate anthropometric values in two cohorts of antipsychotic-naïve first-episode episode psychosis (FEP) and correlated them with surrogate markers of the fetal environment such as birth weight (BW) and season of birth. METHODS: BW, season of birth, and anthropometric values from 2 cohorts of FEP patients (Barcelona and Santander) were evaluated. In cohort B, 91 patients, and 110 controls while in cohort S, 644 and 235 were included respectively. RESULTS: Patients were shorter, slimmer, and with lower BMI compared with controls. In both cohorts, patients, and female patients born in winter displayed the shortest height. Regarding BW, height was significantly associated with the interaction of diagnosis and BW in the whole sample and the male subsample. CONCLUSIONS: Our results confirm reduced anthropometric features in FEP at onset while suggesting the influence of winter birth and BW, highlighting the role of early life events in the later outcome of FEP with sex differences.

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.

Preliminary data from a 4-year mirror-image and multicentre study of patients initiating paliperidone palmitate 6-monthly long-acting injectable antipsychotic: the Paliperidone 2 per Year study.

Background: Paliperidone palmitate 6-monthly (PP6M) is the first long-acting antipsychotic injectable (LAI) to allow for only two medication administrations per year, though there is presently limited insight into its effectiveness and potential added value in real clinical practice conditions. Objectives: To present our ongoing study and draw its preliminary data on patient characteristics initiating PP6M and adherence during the first year of treatment. Methods: The paliperidone 2 per year (P2Y) study is a 4-year, multicentre, prospective mirror-image pragmatic study taking place at over 20 different sites in Europe. The mirror period covers 2 years either side of the PP6M LAI initiation. Retrospective data for the previous 2 years are collected for each patient from the electronic health records. Prospective data are recorded at baseline, 6, 12, 18 and 24 months of drug administration and also cover information on concomitant psychiatric medication, relapses, hospital admissions, side effects, discontinuation and its reasons. Meanwhile, here we present preliminary data from the P2Y study at basal and 6-month period (first and second PP6M administration). Results: At the point of PP6M initiation, the most frequent diagnosis was schizophrenia (69%), the clinical global impression scale mean score was 3.5 (moderately markedly ill) and the rate of previous hospital admissions per patient and year was 0.21. PP6M was initiated after a median of 3-4 years on previous treatment: 146 (73%) from paliperidone palmitate 3-monthly, 37 (19%) from paliperidone palmitate 1-monthly and 17 (9%) from other antipsychotics. The mean dose of the first PP6M was 1098.9 mg. The retention rate at 6 months and 1 year of treatment on PP6M in our cohort was 94%. Conclusion: Patient and clinician preference for LAIs with longer dosing intervals was the main reason for PP6M initiation/switching resulting in high treatment persistence. Future data are needed to evaluate the full impact of PP6M in clinical practice.

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.

Intelligence quotient changes over 10 years: Diversity of cognitive profiles in first episode of psychosis and healthy controls.

OBJECTIVE: This study aimed to analyse whether intelligence quotient (IQ) improves, declines, or remains stable over 10 years among FEP patients and healthy subjects. METHODS: A group of FEP patients enrolled in a Program of First Episode Psychosis in Spain called PAFIP, and a sample of Healthy Controls (HC) completed the same neuropsychological battery at baseline and approximately 10 years later, which included the WAIS vocabulary subtest to estimate premorbid IQ and 10-year IQ. Cluster analysis was performed separately in the patient group and the HC group to determine their profiles of intellectual change. RESULTS: One hundred and thirty-seven FEP patients were grouped into five clusters: "Improved low IQ" (9.49 % of patients), "Improved average IQ" (14.6 %), "Preserved low IQ" (17.52 %), "Preserved average IQ" (43.06 %), and "Preserved high IQ" (15.33 %). Ninety HC were grouped into three clusters: "Preserved low IQ" (32.22 % of the HC), "Preserved average IQ" (44.44 %), and "Preserved high IQ" (23.33 %). The first two clusters of FEP patients, characterized by a low IQ, earlier age at illness onset, and lower educational attainment, showed a substantial cognitive improvement. The remaining clusters demonstrated cognitive stability. CONCLUSIONS: The FEP patients showed intellectual improvement or stability, but no decline post-onset of psychosis. However, their profiles of intellectual change are more heterogeneous than that of HC over 10 years. Particularly, there is a subgroup of FEP patients with a significant potential for long-term cognitive enhancement.

Cognitive performance at first episode of psychosis and the relationship with future treatment resistance: Evidence from an international prospective cohort study.

BACKGROUND: Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia, with recent research finding systematic biological differences between antipsychotic resistant and responsive patients. Our aim was to determine whether cognitive impairment at first episode significantly differs between future antipsychotic responders and resistant cases. METHODS: Analysis of data from seven international cohorts of first-episode psychosis (FEP) with cognitive data at baseline (N = 683) and follow-up data on antipsychotic treatment response: 605 treatment responsive and 78 treatment resistant cases. Cognitive measures were grouped into seven cognitive domains based on the pre-existing literature. We ran multiple imputation for missing data and used logistic regression to test for associations between cognitive performance at FEP and treatment resistant status at follow-up. RESULTS: On average patients who were future classified as treatment resistant reported poorer performance across most cognitive domains at baseline. Univariate logistic regressions showed that antipsychotic treatment resistance cases had significantly poorer IQ/general cognitive functioning at FEP (OR = 0.70, p = .003). These findings remained significant after adjusting for additional variables in multivariable analyses (OR = 0.76, p = .049). CONCLUSIONS: Although replication in larger studies is required, it appears that deficits in IQ/general cognitive functioning at first episode are associated with future treatment resistance. Cognitive variables may be able to provide further insight into neurodevelopmental factors associated with treatment resistance or act as early predictors of treatment resistance, which could allow prompt identification of refractory illness and timely interventions.

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

Polygenic risk scores enhance prediction of body mass index increase in individuals with a first episode of psychosis.

BACKGROUND: Individuals with a first episode of psychosis (FEP) show rapid weight gain during the first months of treatment, which is associated with a reduction in general physical health. Although genetics is assumed to be a significant contributor to weight gain, its exact role is unknown. METHODS: We assembled a population-based FEP cohort of 381 individuals that was split into a Training (n = 224) set and a Validation (n = 157) set to calculate the polygenic risk score (PRS) in a two-step process. In parallel, we obtained reference genome-wide association studies for body mass index (BMI) and schizophrenia (SCZ) to examine the pleiotropic landscape between the two traits. BMI PRSs were added to linear models that included sociodemographic and clinical variables to predict BMI increase (∆BMI) in the Validation set. RESULTS: The results confirmed considerable shared genetic susceptibility for the two traits involving 449 near-independent genomic loci. The inclusion of BMI PRSs significantly improved the prediction of ∆BMI at 12 months after the onset of antipsychotic treatment by 49.4% compared to a clinical model. In addition, we demonstrated that the PRS containing pleiotropic information between BMI and SCZ predicted ∆BMI better at 3 (12.2%) and 12 months (53.2%). CONCLUSIONS: We prove for the first time that genetic factors play a key role in determining ∆BMI during the FEP. This finding has important clinical implications for the early identification of individuals most vulnerable to weight gain and highlights the importance of examining genetic pleiotropy in the context of medically important comorbidities for predicting future outcomes.

Longitudinal trajectories in negative symptoms and changes in brain cortical thickness: 10-year follow-up study.

BACKGROUND: Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes. AIMS: To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories. METHOD: We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases. RESULTS: Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The F-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data. CONCLUSIONS: Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.

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.

Cross-sectional and longitudinal assessment of the association between DDR1 variants and processing speed in patients with early psychosis and healthy controls.

Recent evidence indicates that DDR1 participates in myelination and that variants of DDR1 are associated with decreased cognitive processing speed (PS) in schizophrenia (SZ). Here, we explored whether DDR1 variants were associated with PS in subjects diagnosed with an early psychosis (EP), a condition often preceding SZ. Data from two Spanish independent samples (from Reus and Santander) including patients with EP (n = 75 and n = 312, respectively) and healthy controls (HCs; n = 57 and n = 160) were analyzed. The Trail Making Test part A was used to evaluate PS. Participants underwent genotyping to identify DDR1 variants rs1264323 and rs2267641. Cross-sectional data were analyzed with general linear models and longitudinal data were analyzed using mixed models. We examined the combined rs1264323AA-rs2267641AC/CC genotypes (an SZ-risk combination) on PS. The SZ-risk combined genotypes were associated with increased PS in EP patients but not in HCs in the cross-sectional analysis. In the longitudinal analysis, the SZ-risk combined genotypes were significantly associated with increased PS in both HCs and EP patients throughout the 10-year follow-up but no genotype × time interaction was observed. These results provide further evidence that DDR1 is involved in cognition and should be replicated with other samples.

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.

Sex differences in cognitive reserve among first episode of psychosis patients.

INTRODUCTION: Cognitive reserve (CR) has recently been considered a key factor in the onset of a first episode of psychosis (FEP). However, the differences in CR in FEP patients according to sex have not yet been investigated. MATERIAL AND METHODS: CR was estimated among 443 FEP patients (246 men and 197 women) and 156 healthy controls (96 men and 60 women) by using the proxies premorbid IQ, years of education and employment status. A neuropsychological battery was administrated to measure neurocognitive specific domains. Analyses of variance were used to make comparisons between groups. RESULTS: FEP women had greater CR than FEP men. This circumstance was not observed in healthy controls. Among the group of patients with low CR, FEP women outperformed FEP men in the cognitive domains verbal memory and processing speed. Meanwhile, among the FEP patients with high CR, men showed better performance in attention than women. CONCLUSIONS: Differences in CR observed between FEP men and women could be related to a number of specific factors, such as, age at illness onset, education level, and variability in performance in verbal memory, processing speed, and attention domains. These results provide background information about CR in FEP patients that will be useful in the design of sex specific cognitive remediation interventions.

Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium.

INTRODUCTION: Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR. METHODS: We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.d. = 3.20) for secondary data analysis. We identified a list of potential predictors from clinical and demographic data recorded at first-episode. These potential predictors were entered in two models: a multivariable logistic regression to identify which were independently associated with TR and a penalised logistic regression, which performed variable selection, to produce a parsimonious prediction model. This model was internally validated using a 5-fold, 50-repeat cross-validation optimism-correction. RESULTS: Our sample consisted of N = 2216 participants of which 385 (17 %) developed TR. Younger age of psychosis onset and fewer years in education were independently associated with increased odds of developing TR. The prediction model selected 7 out of 17 variables that, when combined, could quantify the risk of being TR better than chance. These included age of onset, years in education, gender, BMI, relationship status, alcohol use, and positive symptoms. The optimism-corrected area under the curve was 0.59 (accuracy = 64 %, sensitivity = 48 %, and specificity = 76 %). IMPLICATIONS: Our findings show that treatment resistance can be predicted, at first-episode of psychosis. Pending a model update and external validation, we demonstrate the potential value of prediction models for TR.